RU2448976C2 - Hcv/hiv inhibitors and their application - Google Patents

Hcv/hiv inhibitors and their application Download PDF

Info

Publication number
RU2448976C2
RU2448976C2 RU2008144299/04A RU2008144299A RU2448976C2 RU 2448976 C2 RU2448976 C2 RU 2448976C2 RU 2008144299/04 A RU2008144299/04 A RU 2008144299/04A RU 2008144299 A RU2008144299 A RU 2008144299A RU 2448976 C2 RU2448976 C2 RU 2448976C2
Authority
RU
Russia
Prior art keywords
alkyl
group
cycloalkyl
substituted
heterocyclyl
Prior art date
Application number
RU2008144299/04A
Other languages
Russian (ru)
Other versions
RU2008144299A (en
Inventor
Трикси БРАНДЛЬ (CH)
Трикси Брандль
Цзипин ФУ (US)
Цзипин Фу
Франсуа ЛЕНУАР (US)
Франсуа Ленуар
Дейвид Томас ПАРКЕР (US)
Дейвид Томас Паркер
Майкл ПАТЕЙН (US)
Майкл ПАТЕЙН
Бранко РАДЕТИЧ (US)
Бранко Радетич
Пракаш РАМАН (US)
Пракаш Раман
Паскаль РИГОЛЛЬЕ (FR)
Паскаль Риголлье
Мохиндра СИПЕРСАУД (US)
Мохиндра Сиперсауд
Оливер ЗИМИК (CH)
Оливер Зимик
Арегаен ЙИФРЮ (US)
Арегаен ЙИФРЮ
Руи ЧЖЭН (US)
Руи Чжэн
Original Assignee
Новартис Аг
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=38617501&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=RU2448976(C2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Новартис Аг filed Critical Новартис Аг
Publication of RU2008144299A publication Critical patent/RU2008144299A/en
Application granted granted Critical
Publication of RU2448976C2 publication Critical patent/RU2448976C2/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/96—Spiro-condensed ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/07—Tetrapeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/06—Tripeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
    • C07D491/20—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06139—Dipeptides with the first amino acid being heterocyclic
    • C07K5/06165—Dipeptides with the first amino acid being heterocyclic and Pro-amino acid; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0802—Tripeptides with the first amino acid being neutral
    • C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
    • C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0802—Tripeptides with the first amino acid being neutral
    • C07K5/0812—Tripeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
    • C07K5/101—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1016—Tetrapeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Abstract

FIELD: medicine, pharmaceutics.
SUBSTANCE: in claim described are organic compounds of formula I
Figure 00000345
where radicals are given in description, which are applicable for elimination, prevention or alleviation of one or more symptoms, associated with HCV disorders.
EFFECT: obtaining pharmaceutical composition which possesses inhibiting activity with respect to NS3-4 HCV serinprotease, including formula I compound and pharmaceutically acceptable carrier.
30 cl, 25 ex, 2 tbl

Description

Текст описания приведен в факсимильном виде.

Figure 00000001
Figure 00000002
Figure 00000003
Figure 00000004
Figure 00000005
Figure 00000006
Figure 00000007
Figure 00000008
Figure 00000009
Figure 00000010
Figure 00000011
Figure 00000012
Figure 00000013
Figure 00000014
Figure 00000015
Figure 00000016
Figure 00000017
Figure 00000018
Figure 00000019
Figure 00000020
Figure 00000021
Figure 00000022
Figure 00000023
Figure 00000024
Figure 00000025
Figure 00000026
Figure 00000027
Figure 00000028
Figure 00000029
Figure 00000030
Figure 00000031
Figure 00000032
Figure 00000033
Figure 00000034
Figure 00000035
Figure 00000036
Figure 00000037
Figure 00000038
Figure 00000039
Figure 00000040
Figure 00000041
Figure 00000042
Figure 00000043
Figure 00000044
Figure 00000045
Figure 00000046
Figure 00000047
Figure 00000048
Figure 00000049
Figure 00000050
Figure 00000051
Figure 00000052
Figure 00000053
Figure 00000054
Figure 00000055
Figure 00000056
Figure 00000057
Figure 00000058
Figure 00000059
Figure 00000060
Figure 00000061
Figure 00000062
Figure 00000063
Figure 00000064
Figure 00000065
Figure 00000066
Figure 00000067
Figure 00000068
Figure 00000069
Figure 00000070
Figure 00000071
Figure 00000072
Figure 00000073
Figure 00000074
Figure 00000075
Figure 00000076
Figure 00000077
Figure 00000078
Figure 00000079
Figure 00000080
Figure 00000081
Figure 00000082
Figure 00000083
Figure 00000084
Figure 00000085
Figure 00000086
Figure 00000087
Figure 00000088
Figure 00000089
Figure 00000090
Figure 00000091
Figure 00000092
Figure 00000093
Figure 00000094
Figure 00000095
Figure 00000096
Figure 00000097
Figure 00000098
Figure 00000099
Figure 00000100
Figure 00000101
Figure 00000102
Figure 00000103
Figure 00000104
Figure 00000105
Figure 00000106
Figure 00000107
Figure 00000108
Figure 00000109
Figure 00000110
Figure 00000111
Figure 00000112
Figure 00000113
Figure 00000114
Figure 00000115
Figure 00000116
Figure 00000117
Figure 00000118
Figure 00000119
Figure 00000120
Figure 00000121
Figure 00000122
Figure 00000123
Figure 00000124
Figure 00000125
Figure 00000126
Figure 00000127
Figure 00000128
Figure 00000129
Figure 00000130
Figure 00000131
Figure 00000132
Figure 00000133
Figure 00000134
Figure 00000135
Figure 00000136
Figure 00000137
Figure 00000138
Figure 00000139
Figure 00000140
Figure 00000141
Figure 00000142
Figure 00000143
Figure 00000144
Figure 00000145
Figure 00000146
Figure 00000147
Figure 00000148
Figure 00000149
Figure 00000150
Figure 00000151
Figure 00000152
Figure 00000153
Figure 00000154
Figure 00000155
Figure 00000156
Figure 00000157
Figure 00000158
Figure 00000159
Figure 00000160
Figure 00000161
Figure 00000162
Figure 00000163
Figure 00000164
Figure 00000165
Figure 00000166
Figure 00000167
Figure 00000168
Figure 00000169
Figure 00000170
Figure 00000171
Figure 00000172
Figure 00000173
Figure 00000174
Figure 00000175
Figure 00000176
Figure 00000177
Figure 00000178
Figure 00000179
Figure 00000180
Figure 00000181
Figure 00000182
Figure 00000183
Figure 00000184
Figure 00000185
Figure 00000186
Figure 00000187
Figure 00000188
Figure 00000189
Figure 00000190
Figure 00000191
Figure 00000192
Figure 00000193
Figure 00000194
Figure 00000195
Figure 00000196
Figure 00000197
Figure 00000198
Figure 00000199
Figure 00000200
Figure 00000201
Figure 00000202
Figure 00000203
Figure 00000204
Figure 00000205
Figure 00000206
Figure 00000207
Figure 00000208
Figure 00000209
Figure 00000210
Figure 00000211
Figure 00000212
Figure 00000213
Figure 00000214
Figure 00000215
Figure 00000216
Figure 00000217
Figure 00000218
Figure 00000219
Figure 00000220
Figure 00000221
Figure 00000222
Figure 00000223
Figure 00000224
Figure 00000225
Figure 00000226
Figure 00000227
Figure 00000228
Figure 00000229
Figure 00000230
Figure 00000231
Figure 00000232
Figure 00000233
Figure 00000234
Figure 00000235
Figure 00000236
Figure 00000237
Figure 00000238
Figure 00000239
Figure 00000240
Figure 00000241
Figure 00000242
Figure 00000243
Figure 00000244
Figure 00000245
Figure 00000246
Figure 00000247
Figure 00000248
Figure 00000249
Figure 00000250
Figure 00000251
Figure 00000252
Figure 00000253
Figure 00000254
Figure 00000255
Figure 00000256
Figure 00000257
Figure 00000258
Figure 00000259
Figure 00000260
Figure 00000261
Figure 00000262
Figure 00000263
Figure 00000264
Figure 00000265
Figure 00000266
Figure 00000267
Figure 00000268
Figure 00000269
Figure 00000270
Figure 00000271
Figure 00000272
Figure 00000273
Figure 00000274
Figure 00000275
Figure 00000276
Figure 00000277
Figure 00000278
Figure 00000279
Figure 00000280
Figure 00000281
Figure 00000282
Figure 00000283
Figure 00000284
Figure 00000285
Figure 00000286
Figure 00000287
Figure 00000288
Figure 00000289
Figure 00000290
Figure 00000291
Figure 00000292
Figure 00000293
Figure 00000294
Figure 00000295
Figure 00000296
Figure 00000297
Figure 00000298
Figure 00000299
Figure 00000300
Figure 00000301
Figure 00000302
Figure 00000303
Figure 00000304
Figure 00000305
Figure 00000306
Figure 00000307
Figure 00000308
Figure 00000309
Figure 00000310
Figure 00000311
Figure 00000312
Figure 00000313
Figure 00000314
Figure 00000315
Figure 00000316
Figure 00000317
Figure 00000318
Figure 00000319
Figure 00000320
Figure 00000321
Figure 00000322
Figure 00000323
Figure 00000324
Figure 00000325
The text of the description is given in facsimile form.
Figure 00000001
Figure 00000002
Figure 00000003
Figure 00000004
Figure 00000005
Figure 00000006
Figure 00000007
Figure 00000008
Figure 00000009
Figure 00000010
Figure 00000011
Figure 00000012
Figure 00000013
Figure 00000014
Figure 00000015
Figure 00000016
Figure 00000017
Figure 00000018
Figure 00000019
Figure 00000020
Figure 00000021
Figure 00000022
Figure 00000023
Figure 00000024
Figure 00000025
Figure 00000026
Figure 00000027
Figure 00000028
Figure 00000029
Figure 00000030
Figure 00000031
Figure 00000032
Figure 00000033
Figure 00000034
Figure 00000035
Figure 00000036
Figure 00000037
Figure 00000038
Figure 00000039
Figure 00000040
Figure 00000041
Figure 00000042
Figure 00000043
Figure 00000044
Figure 00000045
Figure 00000046
Figure 00000047
Figure 00000048
Figure 00000049
Figure 00000050
Figure 00000051
Figure 00000052
Figure 00000053
Figure 00000054
Figure 00000055
Figure 00000056
Figure 00000057
Figure 00000058
Figure 00000059
Figure 00000060
Figure 00000061
Figure 00000062
Figure 00000063
Figure 00000064
Figure 00000065
Figure 00000066
Figure 00000067
Figure 00000068
Figure 00000069
Figure 00000070
Figure 00000071
Figure 00000072
Figure 00000073
Figure 00000074
Figure 00000075
Figure 00000076
Figure 00000077
Figure 00000078
Figure 00000079
Figure 00000080
Figure 00000081
Figure 00000082
Figure 00000083
Figure 00000084
Figure 00000085
Figure 00000086
Figure 00000087
Figure 00000088
Figure 00000089
Figure 00000090
Figure 00000091
Figure 00000092
Figure 00000093
Figure 00000094
Figure 00000095
Figure 00000096
Figure 00000097
Figure 00000098
Figure 00000099
Figure 00000100
Figure 00000101
Figure 00000102
Figure 00000103
Figure 00000104
Figure 00000105
Figure 00000106
Figure 00000107
Figure 00000108
Figure 00000109
Figure 00000110
Figure 00000111
Figure 00000112
Figure 00000113
Figure 00000114
Figure 00000115
Figure 00000116
Figure 00000117
Figure 00000118
Figure 00000119
Figure 00000120
Figure 00000121
Figure 00000122
Figure 00000123
Figure 00000124
Figure 00000125
Figure 00000126
Figure 00000127
Figure 00000128
Figure 00000129
Figure 00000130
Figure 00000131
Figure 00000132
Figure 00000133
Figure 00000134
Figure 00000135
Figure 00000136
Figure 00000137
Figure 00000138
Figure 00000139
Figure 00000140
Figure 00000141
Figure 00000142
Figure 00000143
Figure 00000144
Figure 00000145
Figure 00000146
Figure 00000147
Figure 00000148
Figure 00000149
Figure 00000150
Figure 00000151
Figure 00000152
Figure 00000153
Figure 00000154
Figure 00000155
Figure 00000156
Figure 00000157
Figure 00000158
Figure 00000159
Figure 00000160
Figure 00000161
Figure 00000162
Figure 00000163
Figure 00000164
Figure 00000165
Figure 00000166
Figure 00000167
Figure 00000168
Figure 00000169
Figure 00000170
Figure 00000171
Figure 00000172
Figure 00000173
Figure 00000174
Figure 00000175
Figure 00000176
Figure 00000177
Figure 00000178
Figure 00000179
Figure 00000180
Figure 00000181
Figure 00000182
Figure 00000183
Figure 00000184
Figure 00000185
Figure 00000186
Figure 00000187
Figure 00000188
Figure 00000189
Figure 00000190
Figure 00000191
Figure 00000192
Figure 00000193
Figure 00000194
Figure 00000195
Figure 00000196
Figure 00000197
Figure 00000198
Figure 00000199
Figure 00000200
Figure 00000201
Figure 00000202
Figure 00000203
Figure 00000204
Figure 00000205
Figure 00000206
Figure 00000207
Figure 00000208
Figure 00000209
Figure 00000210
Figure 00000211
Figure 00000212
Figure 00000213
Figure 00000214
Figure 00000215
Figure 00000216
Figure 00000217
Figure 00000218
Figure 00000219
Figure 00000220
Figure 00000221
Figure 00000222
Figure 00000223
Figure 00000224
Figure 00000225
Figure 00000226
Figure 00000227
Figure 00000228
Figure 00000229
Figure 00000230
Figure 00000231
Figure 00000232
Figure 00000233
Figure 00000234
Figure 00000235
Figure 00000236
Figure 00000237
Figure 00000238
Figure 00000239
Figure 00000240
Figure 00000241
Figure 00000242
Figure 00000243
Figure 00000244
Figure 00000245
Figure 00000246
Figure 00000247
Figure 00000248
Figure 00000249
Figure 00000250
Figure 00000251
Figure 00000252
Figure 00000253
Figure 00000254
Figure 00000255
Figure 00000256
Figure 00000257
Figure 00000258
Figure 00000259
Figure 00000260
Figure 00000261
Figure 00000262
Figure 00000263
Figure 00000264
Figure 00000265
Figure 00000266
Figure 00000267
Figure 00000268
Figure 00000269
Figure 00000270
Figure 00000271
Figure 00000272
Figure 00000273
Figure 00000274
Figure 00000275
Figure 00000276
Figure 00000277
Figure 00000278
Figure 00000279
Figure 00000280
Figure 00000281
Figure 00000282
Figure 00000283
Figure 00000284
Figure 00000285
Figure 00000286
Figure 00000287
Figure 00000288
Figure 00000289
Figure 00000290
Figure 00000291
Figure 00000292
Figure 00000293
Figure 00000294
Figure 00000295
Figure 00000296
Figure 00000297
Figure 00000298
Figure 00000299
Figure 00000300
Figure 00000301
Figure 00000302
Figure 00000303
Figure 00000304
Figure 00000305
Figure 00000306
Figure 00000307
Figure 00000308
Figure 00000309
Figure 00000310
Figure 00000311
Figure 00000312
Figure 00000313
Figure 00000314
Figure 00000315
Figure 00000316
Figure 00000317
Figure 00000318
Figure 00000319
Figure 00000320
Figure 00000321
Figure 00000322
Figure 00000323
Figure 00000324
Figure 00000325

Claims (2)

1. Соединение формулы I:
Figure 00000326

или его фармацевтически приемлемая соль или его стереоизомер;
в которой у равен 1;
n равен 1;
R14 обозначает С(O);
R1 выбран из группы, включающей Н и С1-С4-алкил;
R2 выбран из группы, включающей С1-С4-алкил, С(O)С1-С4-алкил, С(O)ОС1-С4-алкил и С3-С6-циклоалкил-С0-С4-алкил;
или R1 и R2 вместе образуют циклопропановое кольцо, где циклопропановое кольцо может быть дополнительно замещено один или более раз;
W также выбран из группы, включающей С(O)-С(O)Н, C(=N-O-R24)-C(O)-аминогруппу, С(O)-С(O)-аминогруппу, C(O)NR24S(O)pR24, C(O)NR24S(O)pN(R24)2 и С(O)-[С(O)]а-гетероциклил, где гетероциклил может быть один или более раз независимо замещен арилом, C1-C4-алкилом, С1-С4-алкилом, замещенным одним или более атомами галогена, или С3-С6-циклоалкилом, где а равно 0 или 1, где каждый R24 независимо выбран из водорода или из группы, включающей С1-С4-алкил, С3-С6-циклоалкил-С0-С4-алкил, замещенный или незамещенный арил и замещенный или незамещенный гетероциклил, каждый из которых может быть один или более раз независимо замещен атомом галогена или C1-C4-алкилом;
V выбран из группы, включающей -Q1-Q2, где Q1 отсутствует, обозначает С(O), N(H), N(С1-С4-алкил), C=N(CN), C=N(SO2CH3), C=NCOH-C1-C4-алкил или C=N-COH, и Q2 обозначает водород или выбран из группы, включающей С1-С4-алкил, O-С1-С4-алкил, NH2, N(Н)-С1-С4-алкил, N(C1-C4-алкил)2, SО2-арил, SO2-С1-С4-алкил, С3-С6-циклоалкил-С0-С4-алкил, арил, гетероарил и гетероциклил, каждый из которых может быть один или более раз независимо замещен атомом галогена, С1-С4-алкилом, C1-C4-алкилом замещенным одним или более атомами галогена, или С3-С6-циклоалкилом;
р равен 0, 1 или 2;
R3 выбран из группы, включающей водород и С1-С4-алкил;
двухвалентный остаток:
Figure 00000327

выбран из группы, включающей:
Figure 00000328
,
Figure 00000329
,
Figure 00000330
,
Figure 00000331
,
Figure 00000332
,
Figure 00000333
,
Figure 00000334
,
Figure 00000335
,
Figure 00000336
,
Figure 00000337
Figure 00000338
,
Figure 00000339
,
Figure 00000340
,
Figure 00000341
,
Figure 00000342
,
Figure 00000343
,
R8, R9 и R10 каждый независимо выбран из группы, включающей водород, С1-С4-алкил и С3-С6-циклоалкил-С0-С4-алкил;
R11 обозначает Н;
R12 обозначает С3-С6-циклоалкил; и
R13 обозначает Н;
где арил означает 5- и 6-членные моно- или полициклические ароматические группы;
гетероциклил означает 5-10-членный ароматический или неароматический гетероциклил, содержащий от 1 до 4 гетероатомов, выбранных из О, N и S;
и
гетероарил означает моноциклическое или бициклическое кольцо, содержащее до 7 атомов в каждом кольце, в котором по меньшей мере одно кольцо является ароматическим и содержит от 1 до 4 гетероатомов, выбранных из О, N и S.1. The compound of formula I:
Figure 00000326

or a pharmaceutically acceptable salt thereof or a stereoisomer thereof;
in which y is 1;
n is 1;
R 14 is C (O);
R 1 is selected from the group consisting of H and C 1 -C 4 alkyl;
R 2 is selected from the group consisting of C 1 -C 4 -alkyl, C (O) C 1 -C 4 -alkyl, C (O) OC 1 -C 4 -alkyl and C 3 -C 6 -cycloalkyl-C 0 - C 4 -alkyl;
or R 1 and R 2 together form a cyclopropane ring, where the cyclopropane ring may be further substituted one or more times;
W is also selected from the group consisting of C (O) —C (O) H, C (= NOR 24 ) —C (O) amino group, C (O) —C (O) amino group, C (O) NR 24 S (O) p R 24 , C (O) NR 24 S (O) p N (R 24 ) 2 and C (O) - [C (O)] a- heterocyclyl, where heterocyclyl may be one or more times independently substituted by aryl, C 1 -C 4 alkyl, C 1 -C 4 alkyl substituted with one or more halogen atoms, or C 3 -C 6 cycloalkyl, where a is 0 or 1, where each R 24 is independently selected from hydrogen or from the group consisting of C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl-C 0 -C 4 alkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl, each of which can is one or more times independently substituted by a halogen atom or C 1 -C 4 alkyl;
V is selected from the group consisting of -Q 1 -Q 2 , where Q 1 is absent, denotes C (O), N (H), N (C 1 -C 4 alkyl), C = N (CN), C = N (SO 2 CH 3 ), C = NCOH-C 1 -C 4 -alkyl or C = N-COH, and Q 2 is hydrogen or is selected from the group consisting of C 1 -C 4 -alkyl, O-C 1 -C 4- alkyl, NH 2 , N (H) -C 1 -C 4 -alkyl, N (C 1 -C 4 -alkyl) 2 , SO 2 -aryl, SO 2 -C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl-C 0 -C 4 -alkyl, aryl, heteroaryl and heterocyclyl, each of which may be independently or independently substituted one or more times by a halogen atom, C 1 -C 4 -alkyl, C 1 -C 4 -alkyl substituted one or more halogen atoms, or C 3 -C 6 cycloalkyl;
p is 0, 1 or 2;
R 3 is selected from the group consisting of hydrogen and C 1 -C 4 alkyl;
divalent residue:
Figure 00000327

selected from the group including:
Figure 00000328
,
Figure 00000329
,
Figure 00000330
,
Figure 00000331
,
Figure 00000332
,
Figure 00000333
,
Figure 00000334
,
Figure 00000335
,
Figure 00000336
,
Figure 00000337
Figure 00000338
,
Figure 00000339
,
Figure 00000340
,
Figure 00000341
,
Figure 00000342
,
Figure 00000343
,
R 8 , R 9 and R 10 are each independently selected from the group consisting of hydrogen, C 1 -C 4 alkyl and C 3 -C 6 cycloalkyl-C 0 -C 4 alkyl;
R 11 is H;
R 12 is C 3 -C 6 cycloalkyl; and
R 13 is H;
where aryl means 5- and 6-membered mono- or polycyclic aromatic groups;
heterocyclyl means a 5-10 membered aromatic or non-aromatic heterocyclyl containing from 1 to 4 heteroatoms selected from O, N and S;
and
heteroaryl means a monocyclic or bicyclic ring containing up to 7 atoms in each ring, in which at least one ring is aromatic and contains from 1 to 4 heteroatoms selected from O, N and S. 2. Фармацевтическая композиция, обладающая ингибирующей активностью в отношении NS3-4 серинпротеазы HCV, включающая соединение по п.1 и фармацевтически приемлемый носитель. 2. A pharmaceutical composition having inhibitory activity against NS3-4 HCV serine protease, comprising the compound of claim 1 and a pharmaceutically acceptable carrier.
RU2008144299/04A 2006-04-11 2007-04-09 Hcv/hiv inhibitors and their application RU2448976C2 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US79131806P 2006-04-11 2006-04-11
US60/791,318 2006-04-11
US86687406P 2006-11-22 2006-11-22
US60/866,874 2006-11-22

Publications (2)

Publication Number Publication Date
RU2008144299A RU2008144299A (en) 2010-05-20
RU2448976C2 true RU2448976C2 (en) 2012-04-27

Family

ID=38617501

Family Applications (1)

Application Number Title Priority Date Filing Date
RU2008144299/04A RU2448976C2 (en) 2006-04-11 2007-04-09 Hcv/hiv inhibitors and their application

Country Status (27)

Country Link
US (4) US7825152B2 (en)
EP (2) EP2007789B1 (en)
JP (1) JP5167244B2 (en)
KR (1) KR101059593B1 (en)
CN (1) CN101466727B (en)
AR (1) AR060405A1 (en)
AU (1) AU2007249668B2 (en)
BR (1) BRPI0710878A2 (en)
CA (1) CA2643680A1 (en)
CL (1) CL2007001005A1 (en)
CR (1) CR10336A (en)
EC (1) ECSP088811A (en)
ES (1) ES2543840T3 (en)
HK (1) HK1126798A1 (en)
IL (1) IL194434A0 (en)
MA (1) MA30392B1 (en)
MX (1) MX2008013119A (en)
MY (1) MY147247A (en)
NO (1) NO20084749L (en)
NZ (1) NZ571826A (en)
PE (2) PE20080072A1 (en)
RU (1) RU2448976C2 (en)
SG (1) SG173368A1 (en)
TN (1) TNSN08400A1 (en)
TW (1) TWI341207B (en)
UA (1) UA100666C2 (en)
WO (1) WO2007133865A2 (en)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2305695A3 (en) 2005-07-25 2011-07-27 Intermune, Inc. Macrocyclic inhibitors of Hepatitis C virus replication
BRPI0617274A2 (en) 2005-10-11 2011-07-19 Intermune Inc compounds and methods for inhibiting hepatitis c viral replication
CN101466727B (en) 2006-04-11 2012-10-17 诺瓦提斯公司 Hcv/hiv inhibitor and their uses
RU2008152171A (en) 2006-07-05 2010-08-10 Интермьюн, Инк. (Us) NEW HEPATITIS C VIRAL REPLICATION INHIBITORS
EP2185524A1 (en) * 2007-05-10 2010-05-19 Intermune, Inc. Novel peptide inhibitors of hepatitis c virus replication
KR101396696B1 (en) * 2007-10-10 2014-05-16 노파르티스 아게 Spiropyrrolidines and their use against hcv and hiv infection
CA2722858C (en) 2008-04-30 2017-08-29 Siemens Medical Solutions Usa, Inc. Substrate based pet imaging agents
US20090285774A1 (en) * 2008-05-15 2009-11-19 Bristol-Myers Squibb Company Hepatitis C Virus Inhibitors
US8188137B2 (en) 2008-08-15 2012-05-29 Avila Therapeutics, Inc. HCV protease inhibitors and uses thereof
US8512690B2 (en) * 2009-04-10 2013-08-20 Novartis Ag Derivatised proline containing peptide compounds as protease inhibitors
US20110182850A1 (en) * 2009-04-10 2011-07-28 Trixi Brandl Organic compounds and their uses
KR20140000689A (en) * 2010-10-08 2014-01-03 노파르티스 아게 Salts and polymorphs of sulfamide ns3 inhibitors
AU2011311880B2 (en) 2010-10-08 2014-07-24 Novartis Ag Vitamin E formulations of sulfamide NS3 inhibitors
WO2013025858A1 (en) * 2011-08-16 2013-02-21 Glaxosmithkline Llc 5-benzyl-n-phenyethyl-1,3,4-oxadiazole-2-carboxamide derivatives
EP2871181B1 (en) * 2013-11-12 2016-10-05 Acousia Therapeutics GmbH Novel Compounds for Regeneration of Terminally-Differentiated Cells and tissues
CN105769860A (en) * 2016-04-18 2016-07-20 乔海灵 Application of clomethiazole as medicine for preventing and treating liver and esophageal disease
WO2017222915A1 (en) 2016-06-21 2017-12-28 Inception 4, Inc. Heterocyclic prolinamide derivatives
US10526315B2 (en) 2016-06-21 2020-01-07 Orion Ophthalmology LLC Carbocyclic prolinamide derivatives
JP2019524807A (en) * 2016-08-08 2019-09-05 シグナム バイオサイエンシーズ， インコーポレイテッド Pharmaceutical dosage forms and uses thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2004137480A (en) * 2002-05-20 2005-08-10 Бристол-Маерс Сквибб Компани (Us) Hepatitis C Virus Inhibitors
RU2004133044A (en) * 2002-04-11 2006-01-27 Вертекс Фармасьютикалз Инкорпорейтед (Us) SERINE PROTEASES INHIBITORS, IN PARTICULAR, NS3-NS4A HCV PROTEASES
RU2006105002A (en) * 2003-07-18 2006-08-27 Вертекс Фармасьютикалз Инкорпорейтед (Us) Inhibitors of serine proteases, in particular, HC-3-HC4A proteases

Family Cites Families (131)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3798209A (en) 1971-06-01 1974-03-19 Icn Pharmaceuticals 1,2,4-triazole nucleosides
USRE29835E (en) 1971-06-01 1978-11-14 Icn Pharmaceuticals 1,2,4-Triazole nucleosides
US4917888A (en) 1985-06-26 1990-04-17 Cetus Corporation Solubilization of immunotoxins for pharmaceutical compositions using polymer conjugation
US4766106A (en) 1985-06-26 1988-08-23 Cetus Corporation Solubilization of proteins for pharmaceutical compositions using polymer conjugation
JP2514950B2 (en) 1986-03-10 1996-07-10 エフ・ホフマン―ラ ロシユ アーゲー Chemically modified protein, its production method and intermediate
US5041426A (en) 1987-12-21 1991-08-20 Brigham Young University Immune system enhancing 3-β-d-ribofuranosylthiazolo[4,5-d]pyridimine nucleosides and nucleotides
DE3803225A1 (en) * 1988-02-04 1989-08-17 Hoechst Ag AMINO ACID AMIDE WITH PSYCHOTROPIC EFFECT, METHOD FOR THE PRODUCTION THEREOF, AGENTS CONTAINING THE SAME AND THEIR USE
KR0148748B1 (en) 1988-09-16 1998-08-17 장 크라메르, 한스 루돌프 하우스 A multiphase cyclosporin composition
US5026687A (en) 1990-01-03 1991-06-25 The United States Of America As Represented By The Department Of Health And Human Services Treatment of human retroviral infections with 2',3'-dideoxyinosine alone and in combination with other antiviral compounds
AU7675491A (en) 1990-04-04 1991-10-30 Chiron Corporation Hepatitis c virus protease
DK0527815T3 (en) 1990-04-06 2000-11-06 Genelabs Tech Inc Hepatitis C virus epitope
SK278808B6 (en) 1990-11-02 1998-03-04 Novartis Ag Cyclosporines, their use at the preparation of drug for treating and preventing aids, preparation method thereof and fungal strains useable at this method
US5595732A (en) 1991-03-25 1997-01-21 Hoffmann-La Roche Inc. Polyethylene-protein conjugates
US5610054A (en) 1992-05-14 1997-03-11 Ribozyme Pharmaceuticals, Inc. Enzymatic RNA molecule targeted against Hepatitis C virus
US5382657A (en) 1992-08-26 1995-01-17 Hoffmann-La Roche Inc. Peg-interferon conjugates
EP0627406B1 (en) 1992-10-21 1998-10-28 Yoshitomi Pharmaceutical Industries, Ltd. 2-amino-1,3-propanediol compound and immunosuppressant
KR100360964B1 (en) 1992-12-29 2002-11-22 아보트 러보러터리즈 Processes for preparing the intermediates of the retroviral protease inhibiting compounds
WO1994019012A2 (en) 1993-02-24 1994-09-01 Wang Jui H Compositions and methods of application of reactive antiviral polymers
WO1995003056A1 (en) 1993-07-19 1995-02-02 Tokyo Tanabe Company Limited Hepatitis c virus proliferation inhibitor
PT730470E (en) 1993-11-10 2002-08-30 Enzon Inc IMPROVED INTERFERENCE-POLYMER CONJUGATES
DE4415539C2 (en) 1994-05-03 1996-08-01 Osama Dr Dr Med Omer Plants with virustatic and antiviral effects
DE69524962D1 (en) 1994-08-22 2002-02-14 Welfide Corp BENZENE DERIVATIVES AND THEIR MEDICAL USE
DE4432623A1 (en) 1994-09-14 1996-03-21 Huels Chemische Werke Ag Process for bleaching aqueous surfactant solutions
US5824784A (en) 1994-10-12 1998-10-20 Amgen Inc. N-terminally chemically modified protein compositions and methods
JP3786447B2 (en) 1995-03-31 2006-06-14 エーザイ株式会社 Preventive and therapeutic agent for hepatitis C
US6037157A (en) 1995-06-29 2000-03-14 Abbott Laboratories Method for improving pharmacokinetics
US5908621A (en) 1995-11-02 1999-06-01 Schering Corporation Polyethylene glycol modified interferon therapy
US6054472A (en) 1996-04-23 2000-04-25 Vertex Pharmaceuticals, Incorporated Inhibitors of IMPDH enzyme
US5807876A (en) 1996-04-23 1998-09-15 Vertex Pharmaceuticals Incorporated Inhibitors of IMPDH enzyme
AU2064297A (en) 1996-02-29 1997-09-16 Immusol, Inc Hepatitis c virus ribozymes
US5633388A (en) 1996-03-29 1997-05-27 Viropharma Incorporated Compounds, compositions and methods for treatment of hepatitis C
US5830905A (en) 1996-03-29 1998-11-03 Viropharma Incorporated Compounds, compositions and methods for treatment of hepatitis C
HUP0004421A3 (en) 1996-04-23 2002-10-28 Vertex Pharmaceuticals Inc Cam Urea derivatives and pharmaceutical compositions containing them, use thereof for the treatment of deseases mediated by impdh enzyme
US5990276A (en) 1996-05-10 1999-11-23 Schering Corporation Synthetic inhibitors of hepatitis C virus NS3 protease
US5891874A (en) 1996-06-05 1999-04-06 Eli Lilly And Company Anti-viral compound
US5837257A (en) 1996-07-09 1998-11-17 Sage R&D Use of plant extracts for treatment of HIV, HCV and HBV infections
JP3927630B2 (en) 1996-09-27 2007-06-13 エーザイ・アール・アンド・ディー・マネジメント株式会社 Preventive and therapeutic agents for viral infections
US5922757A (en) 1996-09-30 1999-07-13 The Regents Of The University Of California Treatment and prevention of hepatic disorders
BR9712544B1 (en) 1996-10-18 2013-10-22 SERINE PROTEASE INHIBITORS, PHARMACEUTICAL COMPOSITION UNDERSTANDING THE SAME AND ITS USES
GB9623908D0 (en) 1996-11-18 1997-01-08 Hoffmann La Roche Amino acid derivatives
IL119833A (en) 1996-12-15 2001-01-11 Lavie David Hypericum perforatum extracts for the preparation of pharmaceutical compositions for the treatment of hepatitis
EP0966465B1 (en) 1997-03-14 2003-07-09 Vertex Pharmaceuticals Incorporated Inhibitors of impdh enzyme
US6214873B1 (en) 1997-04-04 2001-04-10 Welfide Corporation 2-aminopropane-1,3-diol compounds, medicinal use thereof, and intermediates in synthesizing the same
US6004933A (en) 1997-04-25 1999-12-21 Cortech Inc. Cysteine protease inhibitors
KR100630506B1 (en) 1997-06-30 2006-09-29 메르츠 파마 게엠베하 운트 코. 카가아 1-amino-alkylcyclohexane compounds as nmda receptor antagonists, pharmaceutical compositions comprising the same and method of treating therewith
EP1012180B1 (en) 1997-08-11 2004-12-01 Boehringer Ingelheim (Canada) Ltd. Hepatitis c inhibitor peptide analogues
EP1058686B1 (en) 1998-02-25 2006-11-02 Emory University 2'-fluoronucleosides
GB9806815D0 (en) 1998-03-30 1998-05-27 Hoffmann La Roche Amino acid derivatives
US6323180B1 (en) 1998-08-10 2001-11-27 Boehringer Ingelheim (Canada) Ltd Hepatitis C inhibitor tri-peptides
WO2000009531A2 (en) 1998-08-10 2000-02-24 Novirio Pharmaceuticals Limited β-L-2'-DEOXY-NUCLEOSIDES FOR THE TREATMENT OF HEPATITIS B
EE200100492A (en) 1999-03-19 2002-12-16 Vertex Pharmaceuticals Incorporated IMPDH inhibitors
BR0009564A (en) 1999-04-07 2002-01-08 Pfizer Prod Inc Use of cyp2d6 inhibitors in combination therapies
CN1387606A (en) 1999-09-06 2002-12-25 创新内燃机技术股份有限公司 Internal combustion engine for motor vehicle and method for operating same
US6566365B1 (en) 1999-11-04 2003-05-20 Biochem Pharma Inc. Method for the treatment of Flaviviridea viral infection using nucleoside analogues
EA200200778A1 (en) 2000-02-18 2003-06-26 Шайре Байокем Инк. METHOD OF TREATMENT OR PREVENTION OF HEPATITIS C INFECTION IN THE ORGANISM ORGANISM, PHARMACEUTICAL COMPOSITION AGAINST FLAVIVIRUS, CONNECTION OF FORMULA Ib - AN ACTIVE AGENT FOR THE TREATMENT OR PREVENTION OF EFFECTECH EFFECTURES Ib - AN ACTIVE AGENT FOR THE TREATMENT OR PREVENTION INEKEKHEKUSA Ib - AN ACTIVE AGENT FOR THE TREATMENT OR PROTECTION
BR0110023A (en) 2000-04-13 2003-12-30 Pharmasset Ltd Substituted 3'-or-2 'nucleoside derivatives for treatment of hepatitis virus infections
MY164523A (en) 2000-05-23 2017-12-29 Univ Degli Studi Cagliari Methods and compositions for treating hepatitis c virus
EP1294735A2 (en) 2000-05-26 2003-03-26 Novirio Pharmaceuticals Limited Methods and compositions for treating flaviviruses and pestiviruses
US6875751B2 (en) 2000-06-15 2005-04-05 Idenix Pharmaceuticals, Inc. 3′-prodrugs of 2′-deoxy-β-L-nucleosides
KR100812578B1 (en) 2000-07-13 2008-03-13 상꾜 가부시키가이샤 Amino alcohol derivatives
RU2003105221A (en) 2000-07-21 2004-09-20 Шеринг Корпорейшн (US) NEW PEPTIDES AS INHIBITORS OF NS3-SERIN PROTEASES OF HEPATITIS C VIRUS
AU2001276988B2 (en) * 2000-07-21 2007-01-25 Dendreon Corporation Peptides as NS3-serine protease inhibitors of hepatitis C virus
US7244721B2 (en) 2000-07-21 2007-07-17 Schering Corporation Peptides as NS3-serine protease inhibitors of hepatitis C virus
EP1301527A2 (en) 2000-07-21 2003-04-16 Corvas International, Inc. Peptides as ns3-serine protease inhibitors of hepatitis c virus
AR029851A1 (en) 2000-07-21 2003-07-16 Dendreon Corp NEW PEPTIDES AS INHIBITORS OF NS3-SERINA PROTEASA DEL VIRUS DE HEPATITIS C
AU2001255070A1 (en) 2000-08-28 2002-03-13 Jin-Sub Kim Generator of two-wheeled vehicle and lighting system thereby
US20030008841A1 (en) 2000-08-30 2003-01-09 Rene Devos Anti-HCV nucleoside derivatives
SV2003000617A (en) 2000-08-31 2003-01-13 Lilly Co Eli INHIBITORS OF PROTEASA PEPTIDOMIMETICA REF. X-14912M
JP2004507552A (en) 2000-08-31 2004-03-11 メルク　エンド　カムパニー　インコーポレーテッド Phosphate derivatives as immunomodulators
KR101201552B1 (en) 2000-10-18 2012-11-15 파마셋 인코포레이티드 Modified nucleosides for treatment of viral infections and abnormal cellular proliferation
BR0115447A (en) 2000-11-20 2005-10-18 Bristol Myers Squibb Co Hepatitis C Tripeptide Inhibitors
WO2002048172A2 (en) 2000-12-12 2002-06-20 Schering Corporation Diaryl peptides as ns3-serine protease inhibitors of hepatits c virus
AU2002230763A1 (en) 2000-12-13 2008-01-03 Bristol-Myers Squibb Pharma Company Inhibitors of hepatitis c virus ns3 protease
US6727366B2 (en) 2000-12-13 2004-04-27 Bristol-Myers Squibb Pharma Company Imidazolidinones and their related derivatives as hepatitis C virus NS3 protease inhibitors
AU2002232660A1 (en) 2000-12-15 2002-06-24 Pharmasset Ltd. Antiviral agents for treatment of flaviviridae infections
RS50236B (en) 2001-01-22 2009-07-15 Merck & Co.Inc., Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase
DE10102928B4 (en) 2001-01-23 2004-03-04 Infineon Technologies Ag Viterbi decoder and method for decoding
ATE314383T1 (en) 2001-03-26 2006-01-15 Novartis Pharma Gmbh 2-AMINO-PROPANOL DERIVATIVES
JP2002316985A (en) 2001-04-20 2002-10-31 Sankyo Co Ltd Benzothiophene derivative
DE60235900D1 (en) 2001-09-27 2010-05-20 Kyorin Seiyaku Kk OSUPPRESSIVUM
KR100913269B1 (en) 2001-09-27 2009-08-21 교린 세이야꾸 가부시키 가이샤 Diaryl sulfide derivative, addition salt thereof, and immunosuppressant
EP1435974A4 (en) * 2001-09-28 2006-09-06 Idenix Cayman Ltd Methods and compositions for treating hepatitis c virus using 4'-modified nucleosides
CN101033242A (en) 2001-11-27 2007-09-12 安那迪斯药品股份有限公司 Antenna system for a level measurement apparatus
US6973322B2 (en) 2001-12-22 2005-12-06 International Business Machines Corporation Personal travel agent using push services
EP1575964B1 (en) 2002-01-18 2009-11-11 Merck & Co., Inc. N-(benzyl)aminoalkyl carboxylate, phosphinates, phosphonates and tetrazoles as edg receptor agonists
ATE441654T1 (en) 2002-01-18 2009-09-15 Merck & Co Inc EDG RECEPTOR AGONISTS
MXPA04007163A (en) 2002-01-23 2004-10-29 Schering Corp Proline compounds as ns3-serine protease inhibitors for use in treatment of hepatites c virus infection.
KR20050035194A (en) 2002-06-28 2005-04-15 이데닉스 (케이만) 리미티드 2'-c-methyl-3'-o-l-valine ester ribofuranosyl cytidine for treatment of flaviviridae infections
CA2513213C (en) 2003-01-22 2013-07-30 Human Genome Sciences, Inc. Albumin fusion proteins
RU2375350C2 (en) 2003-06-04 2009-12-10 Смитклайн Бичам Корпорейшн Nitrogen-containing heteroaryl derivatives
EP1633711B1 (en) 2003-06-17 2010-11-24 Schering Corporation Process and intermediates for the preparation of (1r,2s,5s)-6,6-dimethyl-3-azabicyclo[3,1,0]hexane-2-carboxylates or salts thereof
CN1829709A (en) 2003-08-01 2006-09-06 健亚生物科技公司 Bicyclic imidazol derivatives against flaviviridae
JP4527722B2 (en) 2003-08-26 2010-08-18 シェーリング コーポレイション Novel peptidomimetic NS3-serine protease inhibitor of hepatitis C virus
MY148123A (en) 2003-09-05 2013-02-28 Vertex Pharma Inhibitors of serine proteases, particularly hcv ns3-ns4a protease
NZ545536A (en) 2003-09-05 2010-04-30 Anadys Pharmaceuticals Inc TLR7 ligands for the treatment of hepatitis C
TW200526686A (en) 2003-09-18 2005-08-16 Vertex Pharma Inhibitors of serine proteases, particularly HCV NS3-NS4A protease
KR20060130027A (en) * 2003-10-10 2006-12-18 버텍스 파마슈티칼스 인코포레이티드 Inhibitors of serine proteases, particularly hcv ns3-ns4a protease
MXPA06004723A (en) * 2003-10-27 2006-07-05 Vertex Pharma Combinations for hcv treatment.
TW200518746A (en) 2003-12-11 2005-06-16 Schering Corp Novel inhibitors of hepatitis C virus NS3/NS4A serine protease
AU2005212257A1 (en) 2004-02-04 2005-08-25 Vertex Pharmaceuticals Incorporated Inhibitors of serine proteases, particularly HCV NS3-NS4A protease
BRPI0507026A (en) 2004-02-09 2007-04-17 Human Genome Sciences Inc albumin fusion proteins
BRPI0508095A (en) 2004-02-27 2007-07-17 Schering Corp compounds as inhibitors of hepatitis c virus ns3 serine protease
US7635694B2 (en) 2004-02-27 2009-12-22 Schering Corporation Cyclobutenedione-containing compounds as inhibitors of hepatitis C virus NS3 serine protease
KR20060124725A (en) * 2004-02-27 2006-12-05 쉐링 코포레이션 Inhibitors of hepatitis c virus ns3 protease
WO2005087730A1 (en) 2004-02-27 2005-09-22 Schering Corporation 3,4-(cyclopentyl)-fused proline compounds as inhibitors of hepatitis c virus ns3 serine protease
AU2005219824B2 (en) 2004-02-27 2007-11-29 Merck Sharp & Dohme Corp. Novel ketoamides with cyclic p4's as inhibitors of ns3 serine protease of hepatitis c virus
NZ549223A (en) 2004-02-27 2010-10-29 Schering Corp Sulfur compounds as inhibitors of hepatitis C virus NS3 serine protease
AR049635A1 (en) 2004-05-06 2006-08-23 Schering Corp (1R, 2S, 5S) -N - ((1S) -3-AMINO-1- (CYCLLOBUTILMETIL) -2,3-DIOXOPROPIL) -3 - ((2S) -2 - (((((1,1-DIMETILETIL ) AMINO) CARBONIL) AMINO) -3,3-DIMETIL-1-OXOBUTIL) -6,6-DIMETIL-3-AZABICICLO (3.1.0) HEXAN-2-CARBOXAMIDE AS INHIBITOR OF THE NS3 / NS4A SERINA PROTEASA DEL VIRUS DE HEPATITIS C
CN1964985A (en) 2004-06-07 2007-05-16 阿纳迪斯药物公司 3-beta-D-ribofuranosylthiazolo[4,5-d]pyridimine nucleosides and uses thereof
US20060089385A1 (en) 2004-06-08 2006-04-27 Yong Cui Pharmaceutical compositions
AU2005271831A1 (en) * 2004-07-12 2006-02-16 Idun Pharmaceuticals, Inc. Tetrapeptide analogs
WO2006026352A1 (en) 2004-08-27 2006-03-09 Schering Corporation Acylsulfonamide compounds as inhibitors of hepatitis c virus ns3 serine protease
MX2007003812A (en) 2004-10-01 2007-05-24 Vertex Pharma Hcv ns3-ns4a protease inhibition.
PL1793844T3 (en) 2004-10-01 2011-05-31 Debiopharm Sa Use of [d-meala]3-[etval]4-cyclosporin for the treatment of hepatitis c infection
KR101309409B1 (en) 2004-10-01 2013-09-23 싸이넥시스, 인크. 3-ether and 3-thioether substituted cyclosporin derivatives for the treatment and prevention of hepatitis c infection
MY141025A (en) 2004-10-29 2010-02-25 Vertex Pharma Dose forms
WO2006076529A1 (en) 2005-01-14 2006-07-20 Genelabs Technologies, Inc. Indole derivatives for treating viral infections
US20070004635A1 (en) 2005-06-02 2007-01-04 Schering Corporation Method of treating interferon non-responders using HCV protease inhibitor
WO2006130687A2 (en) 2005-06-02 2006-12-07 Schering Corporation Liver/plasma concentration ratio for dosing hepatitis c virus protease inhibitor
WO2006130666A2 (en) 2005-06-02 2006-12-07 Schering Corporation Medicaments and methods combining a hcv protease inhibitor and an akr competitor
WO2006130626A2 (en) 2005-06-02 2006-12-07 Schering Corporation Method for modulating activity of hcv protease through use of a novel hcv protease inhibitor to reduce duration of treatment period
AU2006252519B2 (en) 2005-06-02 2012-08-30 Merck Sharp & Dohme Corp. HCV protease inhibitors in combination with food
US7608592B2 (en) 2005-06-30 2009-10-27 Virobay, Inc. HCV inhibitors
NZ565540A (en) 2005-08-02 2011-06-30 Vertex Pharma Inhibitors of serine proteases
AR055395A1 (en) 2005-08-26 2007-08-22 Vertex Pharma INHIBITING COMPOUNDS OF THE ACTIVITY OF SERINA PROTEASA NS3-NS4A OF HEPATITIS C VIRUS
US20070265281A1 (en) 2006-04-11 2007-11-15 Sylvain Cottens Organic Compounds and Their Uses
CA2648298A1 (en) 2006-04-11 2007-10-25 Novartis Ag Organic compounds and their uses
CN101466727B (en) * 2006-04-11 2012-10-17 诺瓦提斯公司 Hcv/hiv inhibitor and their uses
WO2007120595A2 (en) 2006-04-11 2007-10-25 Novartis Ag Amines for the treatment of hcv
KR101396696B1 (en) * 2007-10-10 2014-05-16 노파르티스 아게 Spiropyrrolidines and their use against hcv and hiv infection
US8512690B2 (en) * 2009-04-10 2013-08-20 Novartis Ag Derivatised proline containing peptide compounds as protease inhibitors

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2004133044A (en) * 2002-04-11 2006-01-27 Вертекс Фармасьютикалз Инкорпорейтед (Us) SERINE PROTEASES INHIBITORS, IN PARTICULAR, NS3-NS4A HCV PROTEASES
RU2004137480A (en) * 2002-05-20 2005-08-10 Бристол-Маерс Сквибб Компани (Us) Hepatitis C Virus Inhibitors
RU2006105002A (en) * 2003-07-18 2006-08-27 Вертекс Фармасьютикалз Инкорпорейтед (Us) Inhibitors of serine proteases, in particular, HC-3-HC4A proteases

Also Published As

Publication number Publication date
TWI341207B (en) 2011-05-01
EP2007789B1 (en) 2015-05-20
US20130149281A1 (en) 2013-06-13
EP2518079A3 (en) 2012-12-12
ECSP088811A (en) 2008-11-27
AU2007249668B2 (en) 2011-04-07
SG173368A1 (en) 2011-08-29
US20100331243A1 (en) 2010-12-30
WO2007133865A2 (en) 2007-11-22
HK1126798A1 (en) 2009-09-11
IL194434A0 (en) 2011-08-01
US20070286842A1 (en) 2007-12-13
UA100666C2 (en) 2013-01-25
PE20080072A1 (en) 2008-03-28
US20120231998A1 (en) 2012-09-13
EP2007789A2 (en) 2008-12-31
BRPI0710878A2 (en) 2015-03-31
TW200815478A (en) 2008-04-01
CN101466727B (en) 2012-10-17
MX2008013119A (en) 2008-10-21
EP2518079A2 (en) 2012-10-31
CN101466727A (en) 2009-06-24
US7825152B2 (en) 2010-11-02
CL2007001005A1 (en) 2008-07-11
RU2008144299A (en) 2010-05-20
US8445527B2 (en) 2013-05-21
AU2007249668A1 (en) 2007-11-22
US8211932B2 (en) 2012-07-03
MY147247A (en) 2012-11-14
CA2643680A1 (en) 2007-11-22
NZ571826A (en) 2012-01-12
KR101059593B1 (en) 2011-08-25
TNSN08400A1 (en) 2010-04-14
CR10336A (en) 2008-12-03
NO20084749L (en) 2008-11-10
WO2007133865A3 (en) 2008-07-10
MA30392B1 (en) 2009-05-04
JP2009533464A (en) 2009-09-17
JP5167244B2 (en) 2013-03-21
KR20080111123A (en) 2008-12-22
AR060405A1 (en) 2008-06-11
ES2543840T3 (en) 2015-08-24
PE20121157A1 (en) 2012-09-14

Similar Documents

Publication Publication Date Title
RU2448976C2 (en) Hcv/hiv inhibitors and their application
RU2495044C2 (en) Protein tyrosine kinase activity inhibitors
RU2371433C2 (en) Phenyl substituted pyrrolidones
AR047076A1 (en) PIRROLOTRIAZINE COMPOUNDS AS THYROSINE KINASE INHIBITORS, PHARMACEUTICAL COMPOSITIONS
EA200970461A1 (en) SUBSTITUTED DERIVATIVES 3-ISOBUTYL-9,10-DIMETOXI-1,3,4,6,7,11b-HEXAHYDRO-2H-PYRIDO [2,1-a] IZOHINOLIN-2-OLA AND RELATED METHODS
AR049646A1 (en) USEFUL SULFAMATE AND SULFAMIDE DERIVATIVES FOR THE TREATMENT OF EPILEPSY AND RELATED DISORDERS
AR057380A1 (en) CHEMICAL COMPOUNDS DERIVED FROM 2-AZETIDINONE AND THERAPEUTIC USE OF THE SAME
HK1110868A1 (en) Heterocyclic compounds as ccr2b antagonists
AR045595A1 (en) USEFUL COMPOSITIONS AS INHIBITORS OF KINASE PROTEINS
AR054482A1 (en) DERIVATIVES OF AZETIDINONE FOR THE TREATMENT OF HYPERLIPIDEMIAS
ECSP066760A (en) DERIVED FROM 4-OXOPIRIMIDINE CONDENSED RINGS
PE20070218A1 (en) AMINO-HYDANTOIN CYCLOALKYL COMPOUNDS AND USE OF THESE FOR THE MODULATION OF ß-SECRETASE
EA200970510A1 (en) HETEROMONOCYCLIC COMPOUND AND ITS APPLICATION
EA200800924A1 (en) NEW CONNECTIONS OWNED WITH INHIBITING ACTIVITY WITH RESPECT TO SODI-DEPENDENT TRANSPORTER
EA200702058A1 (en) NEW PHARMACEUTICAL COMPOUNDS
PE20040937A1 (en) DERIVATIVES OF PYRIDAZIN-3 (2H) -ONE AS INHIBITORS OF PHOSPHODIESTERASE-4 (PDE 4)
AR053120A1 (en) AMINOPIRIDINS AS INHIBITORS OF BETA SECRETASA
EA201000101A1 (en) DERIVATIVES OF PYRIMIDINE 934
EA200401613A1 (en) Drug for cancer treatment
RU2013119129A (en) ORGANIC COMPOUNDS
BRPI0615248A2 (en) derivative having ppar agonist activity
AR060623A1 (en) COMPOUNDS DERIVED FROM 2-AZETIDINONE AND A PREPARATION METHOD
RU2006109004A (en) 7-AMINOalkylidenylheterocyclic quinolones and naphthyridones
AR110443A1 (en) HISTONE METHYLTRANSPHERASES INHIBITORS
CO6230986A2 (en) COMPOSITE OF 4-PYRIDINONE AND ITS USE FOR CANCER

Legal Events

Date Code Title Description
MM4A The patent is invalid due to non-payment of fees

Effective date: 20160410